Apalutamide With or Without Stereotactic Body Radiation in Treating Castration-Resistant Prostate Cancer

NCT03503344 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 175519NCI-2018-00572
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the how well apalutamide with or without stereotactic body radiation therapy work in treating participants with castration-resistant prostate cancer. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using apalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. It is not yet known whether giving apalutamide with or without stereotactic body radiation therapy works better in treating participants with castration-resistant cancer.

Conditions

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Undetectable Serum Prostate-specific Antigen (PSA)

  The primary endpoint for the study is the proportion of participants with undetectable serum PSA (\< 0.2 ng/mL) at 6 months following completion of apalutamide therapy (18 months from date of randomization). Participants who discontinue apalutamide prior to completion of 12 months of therapy for reasons other than disease progression by Prostate Cancer Clinical Trials Working Group (PCWG) criteria, as well as participants who withdraw or are lost to follow up, will be considered unevaluable for this analysis. Participants who discontinue treatment for radiographic or clinical progression, even if occurring prior to receipt of Stereotactic radiation therapy (SBRT) in the experimental arm), would be evaluable for analysis of the primary endpoint.

  Approximately 18 months from date of randomization

Secondary Outcomes (2)

• Median Time to PSA Progression

  Up to 36 months

• Number of Participants With Treatment-related Adverse Events (AEs)

  Up to 36 months

Study Arms (2)

Arm A (apalutamide monotherapy)

EXPERIMENTAL

Participants receive apalutamide PO QD on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Apalutamide

Arm B (apalutamide, SBRT)

EXPERIMENTAL

Participants receive apalutamide PO QD on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Beginning 60 days after first dose of apalutamide, participants also undergo stereotactic body radiation therapy for 1-5 fractions.

Drug: Apalutamide; Radiation: Stereotactic Body Radiation Therapy

Interventions

Apalutamide DRUG

Given PO, 240 mg per day (4 x 60mg tablets)

Also known as: ARN 509, JNJ 56021927

Arm A (apalutamide monotherapy); Arm B (apalutamide, SBRT)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Arm B (apalutamide, SBRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Progressive, castration-resistant prostate cancer demonstrated during continuous antiandrogen therapy (ADT), defined as 3 PSA rises at least 1 week apart, with a minimum PSA \> .05 ng/mL obtained during screening.
• At least one but no more than 5 discrete PSMA-avid radiation fields on baseline PSMA-PET scan; all PSMA-avid lesions in radiation fields must be amenable to SBRT in judgment of treating radiation oncologist; there are no restrictions on site of lesion/radiation fields (e.g. bone, lymph node, prostate, visceral). Equivocal lesions/radiation fields on PSMA PET scan that are not definitive for metastasis will not count towards the limit of 5 radiation fields and will not undergo SBRT
• Surgically or medically castrated, with testosterone levels of \< 50 ng/dL during screening; if the patient is medically castrated, continuous dosing with luteinizing hormone-releasing hormone (LHRH) analogue must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone including post-treatment follow up period
• No prior systemic treatment initiated for the treatment of castration resistant prostate cancer, including abiraterone acetate, enzalutamide, apalutamide, darolutamide, other novel AR or CYP17 antagonist, or docetaxel.
• Patients receiving bone loss prevention treatment with bone-modifying agents (e.g. denosumab, zoledronic acid) must be on stable doses for at least 4 weeks prior to randomization
• Patients who received a first generation anti-androgen (e.g., bicalutamide, flutamide, nilutamide) as most recent treatment must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after washout
• At least 4 weeks or 5 half-lives, whichever is shorter, must have elapsed from the use of any anti-cancer therapy, other than Luteinizing hormone-releasing hormone (LHRH) analog or first generation antiandrogen, prior to randomization
• At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
• Age \> 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
• Resolution of all acute toxic effects of prior therapy or surgical procedure to grade 1 or baseline prior to randomization
• Serum aspartate transaminase (AST) ((serum glutamic oxaloacetic transaminase (SGOT\])) and serum alanine transaminase (ALT) (( serum glutamic pyruvic transaminase (SGPT)) ≤ 2.5 x upper limit of normal (ULN)
• Total serum bilirubin ≤ 1.5 x ULN; in subjects with known or suspected Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, direct bilirubin is ≤ 1.5 x ULN
• Glomerular filtration rate ≥ 45 ml/min based on Cockcroft-Gault equation

You may not qualify if:

• Presence of visceral lesions (e.g. lung, liver) detectable on baseline imaging or bone lesions requiring focal radiation treatment at the time of study entry
• History of seizure or condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system (CNS) or meningeal disease which may require treatment with surgery or radiation therapy
• Concurrent therapy with any of the following (all must have been discontinued or substituted for at least 1 week prior to randomization, except for medications known to lower seizure threshold which must be discontinued or substituted at least 4 weeks prior to randomization)
• Medications known to lower the seizure threshold
• Herbal (e.g., saw palmetto) and non-herbal (e.g., pomegranate) products that may decrease PSA levels
• Systemic (oral/intravenous (IV)/intramuscular (IM)) corticosteroids; patients on chronic stable dose of steroids at an equivalent dose of prednisone ≤ 10 mg daily may be permitted to enroll at the discretion of principal investigator
• Any other experimental treatment on another clinical trial
• Any of the following within 6 months prior to randomization: Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias
• Uncontrolled hypertension at study entry; patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by antihypertensive treatment
• Gastrointestinal disorder affecting absorption
• Secondary malignancy requiring active treatment except for non-melanoma skin cancer and superficial bladder cancer
• Any medical condition that would be a contra-indication to radiation therapy, such as inflammatory bowel disease
• Spinal cord compression or impending spinal cord compression
• Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures

Sponsors & Collaborators

• Janssen Pharmaceuticals: collaborator
• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Interventions

apalutamide; Radiosurgery

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Rahul Aggarwal, MD
• Organization: University of California, San Francisco

Rahul.Aggarwal@ucsf.edu

(415) 476-1000

Study Officials

• Rahul Aggarwal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 19, 2018
• Study Start: December 17, 2019
• Primary Completion: December 31, 2024
• Study Completion: October 31, 2025
• Last Updated: January 21, 2026
• Results First Posted: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)